In some species of primates as well as guinea pigs, infants exhibit a 2-stage, active/passive, response during maternal separation. This second stage (termed despair in primates) of separation from the maternal attachment figure has provided a long-standing animal model for the study of depressive illness. The proposed experiments will test in guinea pig pups the hypotheses that: (1) passive behaviors (crouched stance, eye-closing, and extensive piloerection together with low levels of vocalizing and locomotor activity) observed during prolonged isolation represent what have come to be known as "stress-induced sickness behaviors" (i.e., components of the inflammatory response that can be elicited by stressors as well as immunologic stimuli); and, (2) that the stress-responsive peptide CRF can stimulate inflammatory reactions to produce the passive behavioral responses. Specific Aim 1 will evaluate the first hypothesis by attempting to reverse the passive behavioral responses and increased core temperature observed in isolated guinea pig pups with: (1) infusion into the cerebral venticles of alpha-MSH, an anti-inflammatory peptide; and, (2) systemic administration of indomethacin, an inhibitor of prostaglandin synthesis. Specific Aim 2 will evaluate the second hypothesis by using the same two techniques to attempt to reverse passive behavioral responses produced by injection of CRF. Positive results in the proposed studies would provide an alternative perspective from which to view elements of the classic maternal separation response and would support recent conceptualizations of aspects of depressive symptomatology as behavioral components of the inflammatory response. [unreadable] [unreadable]